Tumor suppressive activity of a variant isoform of manganese superoxide dismutase released by a human liposarcoma cell line

Aldo Mancini, Antonella Borrelli, Antonella Schiattarella, Stefania Fasano, Antonella Occhiello, Alessandra Pica, Peter Sehr, Massimo Tommasino, Jürg P F Nüesch, Jean Rommelaere

Research output: Contribution to journalArticle

Abstract

A cell line derived from a pleiomorphic liposarcoma, named LSA, was previously reported to secrete (a) factor(s) exhibiting oncotoxic properties. The present article describes the isolation, purification and sequence analysis of a protein released by LSA cells into conditioned culture medium. This protein proved to be a variant isoform of manganese superoxide dismutase (MnSOD), hence its designation as LSA-type-MnSOD. This LSA-type-SOD differed from conventional SODs in its secretion by producer cells, contrasting with the normal localization of SODs in the mitochondrial matrix. Interestingly, during the protein purification process, LSA-type-SOD cosegregated with a cytotoxic activity directed against a number of tumor cell lines, as determined under in vitro conditions. This cytopathic effect was most likely due to LSA-type-SOD, since it could be fully reproduced using recombinant SOD that was expressed from cDNA clones isolated from LSA cells mRNA preparations and henceforth designated L-rSOD. In addition to its manifestation in cell lines kept in tissue culture, the oncotoxicity of LSA-type-SOD was further reflected in a remarkable capacity of this protein for suppression of mammary tumors in Balb-C-FRIII mice. Animals subcutaneously injected with L-rSOD in the tumor area showed a complete disruption of established mammary carcinomas, as monitored by nuclear magnetic resonance (NMR) scanning. Moreover, metastatic spreading, which was readily detected in the control group, was suppressed in the treated animals. Altogether these data suggest that LSA-type-SOD interferes with survival and spreading of neoplastically transformed cells and deserves to be future validated as a therapeutic agent against cancer, either alone or in combination with conventional treatments.

Original languageEnglish
Pages (from-to)932-943
Number of pages12
JournalInternational Journal of Cancer
Volume119
Issue number4
DOIs
Publication statusPublished - Aug 15 2006

Keywords

  • Liposarcoma
  • Oncotoxicity
  • Secreted MnSOD-2
  • Tumor suppression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Tumor suppressive activity of a variant isoform of manganese superoxide dismutase released by a human liposarcoma cell line'. Together they form a unique fingerprint.

  • Cite this

    Mancini, A., Borrelli, A., Schiattarella, A., Fasano, S., Occhiello, A., Pica, A., Sehr, P., Tommasino, M., Nüesch, J. P. F., & Rommelaere, J. (2006). Tumor suppressive activity of a variant isoform of manganese superoxide dismutase released by a human liposarcoma cell line. International Journal of Cancer, 119(4), 932-943. https://doi.org/10.1002/ijc.21904